Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease

Introduction Pre-clinical markers of Parkinson’s Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. Methods 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. Results All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Conclusion Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD

Past electron-positron g-2 experiments yielded sharpest bound on CPT violation for point particles

In our past experiments on a single electron and positron we measured the cyclotron and spin-cyclotron difference frequencies omega_c and omega_a and the ratios a = omega_a/ omega_c at omega_c = 141 Ghz for e^- and e^+ and later, only for e^-, also at 164 Ghz. Here, we do extract from these data, as had not done before, a new and very different figure of merit for violation of CPT symmetry, one similar to the widely recognized impressive limit |m_Kaon - m_Antikaon|/m_Kaon < 10^-18 for the K-mesons composed of two quarks. That expression may be seen as comparing experimental relativistic masses of particle states before and after the C, P, T operations had transformed particle into antiparticle. Such a similar figure of merit for a non-composite and quite different lepton, found by us from our Delta a = a^- - a^+ data, was even smaller, h_bar |omega_a^- - omega_a^+|/2m_0 c^2 = |Delta a| h_bar omega_c/2m_0 c^2) < 3(12) 10^-22.Comment: Improved content, Editorially approved for publication in PRL, LATEX file, 5 pages, no figures, 16

Spatial Discrimination Threshold Abnormalities are not Detected in a Pilot Study of DYT6 Dystonia Mutation Carriers

Background: Spatial discrimination thresholds (SDTs) assess somatosensory integration, and provide a window into better understanding the pathophysiology of dystonia. They are abnormal in some focal dystonias, but normal in DYT1 dystonia. It is unknown whether SDTs are altered in DYT6 gene mutation carriers (C). Methods: SDTs were assessed in 17 DYT6 C (including eight manifesting carriers), 15 DYT1 C (including seven manifesting carriers) and 34 controls, using a standardized grating orientation task. Subjects were asked to recognize the orientation of Johnson–Van Boven–Philips (JVP) dome gratings on either index fingertip until 40% or more answers were incorrect. SDTs between indexes were calculated and averaged, with a final SDT assigned to each subject, and tertiles for control SDTs were constructed. Results: SDTs of DYT6 C or DYT1 C were comparable to those of controls, and not more likely to be in the worst tertile (p = 0.8 for DYT6 C vs. controls and p = 1.0 for DYT1 C vs. controls). This was independent of gene expression. Discussion: DYT6 carriers do not have impaired SDTs with the JVP dome paradigm. The normal SDT pattern thus suggests shared sensory physiologic patterns with DYT1 dystonia

Chemical Reaction Dynamics at Surfaces

Contains reports on four research projects.Joint Services Electronics Program Contract DAAL03-92-C-000

DNA Nucleobase Synthesis at Titan Atmosphere Analog by Soft X-rays

Titan, the largest satellite of Saturn, has an atmosphere chiefly made up of N2 and CH4 and includes traces of many simple organic compounds. This atmosphere also partly consists of haze and aerosol particles which during the last 4.5 gigayears have been processed by electric discharges, ions, and ionizing photons, being slowly deposited over the Titan surface. In this work, we investigate the possible effects produced by soft X-rays (and secondary electrons) on Titan aerosol analogs in an attempt to simulate some prebiotic photochemistry. The experiments have been performed inside a high vacuum chamber coupled to the soft X-ray spectroscopy beamline at the Brazilian Synchrotron Light Source, Campinas, Brazil. In-situ sample analyses were performed by a Fourier transform infrared spectrometer. The infrared spectra have presented several organic molecules, including nitriles and aromatic CN compounds. After the irradiation, the brownish-orange organic residue (tholin) was analyzed ex-situ by gas chromatographic (GC/MS) and nuclear magnetic resonance (1H NMR) techniques, revealing the presence of adenine (C5H5N5), one of the constituents of the DNA molecule. This confirms previous results which showed that the organic chemistry on the Titan surface can be very complex and extremely rich in prebiotic compounds. Molecules like these on the early Earth have found a place to allow life (as we know) to flourish.Comment: To appear in Journal of Physical Chemistry A.; Number of pages: 6; Number of Figures: 5; Number of Tables: 1; Number of references:49; Full paper at http://pubs.acs.org/doi/abs/10.1021/jp902824

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Chemical Reaction Dynamics at Surfaces

Contains reports on two research projects with publication lists in each section.Joint Services Electronics Program Contract DAAL03-89-C-0001MIT Energy Laboratory Synthetic Fuels CenterNational Science Foundation Grant CHE 85-08734Petroleum Research Fund Contract 19014-AC

Chemical Reaction Dynamics at Surfaces

Contains reports on three research projects.Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant CHE 90-20623U.S. Department of Energy Grant DE-FG02-89-ER1403

Mechanisms Models and Biomarkers in Amyotrophic Lateral Sclerosis

The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery